1. Monitoring CAC and IMT: A useful clinical tool? Cardiology Service Walter Reed Army Medical Center Walter Reed Army Health Care System NO CONFLICTS TO DISCLOSE Allen J. Taylor MD COL, Medical Corps Professor of Medicine, USUHS Chief of Cardiology

2. How do we monitor successful control of cardiovascular risk? Attainment of risk factor targets BP, LDL-C, HDL-C Use of specific medication classes Compliance with therapeutic lifestyle changes Tobacco, physical activity and diet Inference: Control of risk factors equates to control of the target disease… Atherosclerosis

3. Is the answer within a “global risk” assessment? Multi-variable risk indices are generally not validated for demonstrating the control of cardiovascular risk Due to Concept of exposure duration Measurement error High lifetime risk even in the setting of low near term risk Lloyd-Jones. AJC 2004;94:20-24

4. Is monitoring atherosclerosis the answer? Serial angiographic study in 335 pts, mean age 51, f/u 44 months Waters et al. Circulation 1993;87:1067-1075 QCA progression >15% increase in diameter stenosis 42% 50% increase in adjusted risk for cardiac death/MI P <.001

5. Coronary Atherosclerosis Progression A marker of increased risk for events CLAS: secondary prevention, men, colestipol + niacin vs. placebo Azen et al. Circulation 1996;93:34-41 CAD progression Common (49%) Associated with significantly higher risk for future events P =.03

6. IVUS progression predicts clinical events Essen University: Serial IVUS study of the left main coronary artery in 56 pts undergoing left coronary PCI Erbel and colleagues. Circulation 2004;110:1579 Change in plaque area related to clinical risk factors Most events occurred in those with the greatest progression P+M 25% vs. 6%

7. IMT Progression Rate A marker of increased risk for events CLAS: secondary prevention, men, colestipol/niacin vs. placebo Hodis. Ann Intern Med 1998;128:262 P <.001 Rate of progression is associated with significantly higher risk for future events Predictive power superior to coronary artery progression

8. Therapeutics shown to slow progression of CIMT Lifestyle interventions- exercise Lipid modifying agents- Binding resins, niacin, STATINS, new agents Anti-hypertensives CCB’s,  blockers, ACEI Anti-diabetic agents Metformin, TZD’s Hormonal therapy: HRT

9. Could IMT be used to monitor a patients atherosclerosis extent? Tension between expected IMT progression vs. test reproducibility Annual CIMT progression:.01-.015 mm/y Reproducibility ±.02-.04 mm Most reproducible in common carotid > bulb/internal carotid Extended time-horizon should improve ability to discriminate signal from noise

10. Methods to Improve CIMT Reproducibility Common carotid vs. other segments Collect/analyze images in duplicate Consistent technology, sonographers and readers High frequency imaging Standardization of methods needed

11. Higher Frequency Imaging 7 MHz: 1995 8 MHz: 1999 10 MHz: 1999 13 MHz: 2005

12. Common carotid artery advantageous: obtainable in virtually all Far wall measurements Minimum 7MHz probes Minimum 10 mm length of IMT from well-visualized segment

13. CAC score progression Raggi et al. ATVB. 2004;24(7):1272-7  progression in individuals with events Open issues: Calculation? %/year Volume Determinants uncertain Groups overlap Raggi et al. AJC. 2003;92:827

14. Statin/CAC Paradox: BELLES Raggi et al. Circulation 2005;112:563 LDL control vs. CAC progression over 12 months RCT, n = 615 Atorva 80 vs. prava 40 LDL 92 vs. 129 No difference in CVS ~15%/yr

15. Statin/CAC Paradox: St. Francis Arad et al. J Am Coll Cardiol 2005;46:166 –72 Atorva vs. placebo RCT, n = 1005 With CAC>80 th percentile 4 year CAC progression No difference despite strong trend for event reduction CAC progression: Slightly greater in those with events 44% vs. 33% Unrelated to events

16. ATVB 2005;25:592 In vitro study of statins on AVMF and osteoblasts “Statins inhibit calcification in AVMFs by inhibiting the cholesterol biosynthetic pathway, independent of protein prenylation, but paradoxically stimulate bone cell calcification. “

17. Conclusions Individuals with atherosclerosis progression is associated with heightened risk for cardiovascular events Invasive and noninvasive assessments CIMT: Accurate detection of risk will require that the IMT measurement be reproducible enough and time horizon be long enough to accurately discriminate true progression Progression of CAC >15% per year has been associated with increased risk of CHD events Overlap, determinants, and statin paradox complicate this assessment More study needed